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Effects of gene deletion of the tissue inhibitor of the matrix metalloproteinase-type 1 (TIMP-1) on left ventricular geometry and function in miceAlterations in the expression and activity of the matrix metalloproteinases (MMPs) and the tissue inhibitors of the MMPs (TIMPs) have been implicated in tissue remodeling in a number of disease states. One of the better characterized TIMPs, TIMP-1, has been shown to bind to active MMPs and to regulate the MMP activational process. The goal of this study was to determine whether deletion of the TIMP-1 gene in mice, which in turn would remove TIMP-1 expression in LV myocardium, would produce time-dependent effects on LV geometry and function. Age-matched sibling mice (129Sv) deficient in the TIMP-1 gene (TIMP-1 knock-out (TIMP-1 KO), n=10) and wild-type mice (n=10) underwent comparative echocardiographic studies at 1 and 4 months of age. LV catheterization studies were performed at 4 months and the LV harvested for histomorphometric studies. LV end-diastolic volume and mass increased (18+/-4 and 38+/-3%, respectively, P<0.05) at 4 months in the TIMP-1 KO group; a significant increase compared to wild-type controls (P<0.05). At 4 months, LV and end-diastolic wall stress was increased by over two-fold in the TIMP-1 KO compared to wild type (P<0.05). However, LV systolic pressure and ejection performance were unchanged in the two groups of mice. LV myocyte cross-sectional area was unchanged in the TIMP-1 KO mice compared to controls, but myocardial fibrillar collagen content was reduced. Changes in LV geometry occurred in TIMP-1 deficient mice and these results suggest that constitutive TIMP-1 expression participates in the maintenance of normal LV myocardial structure. Copyright 2000 Academic Press.
Document ID
20040141691
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Roten, L.
(Medical University of South Carolina and Roswell Park Cancer Institute Buffalo, New York, United States)
Nemoto, S.
Simsic, J.
Coker, M. L.
Rao, V.
Baicu, S.
Defreyte, G.
Soloway, P. J.
Zile, M. R.
Spinale, F. G.
Date Acquired
August 22, 2013
Publication Date
January 1, 2000
Publication Information
Publication: Journal of molecular and cellular cardiology
Volume: 32
Issue: 1
ISSN: 0022-2828
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: PO1 HL48788
CONTRACT_GRANT: HL-57952
CONTRACT_GRANT: HL-59165
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Program Biomedical Research and Countermeasures
NASA Discipline Cardiopulmonary

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